Sulfasalazine for ankylosing spondylitis
Abstract
Background
Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown cause and belongs to a group of diseases known as spondyloarthropathies (SpA), which includes reactive arthritis, arthritis/spondylitis in inflammatory bowel disease, psoriatic arthritis/spondylitis and undifferentiated SpA. Non‐steroidal anti‐inflammatory drugs (NSAIDs) have been the main treatment for AS. For those refractory or intolerant to NSAIDs, the disease modifying antirheumatic drugs (DMARDs) have been used as a second line approach. Sulfasalazine (SSZ) is the best studied DMARD in AS, but its efficacy remains unclear.
Objectives
To evaluate the efficacy and toxicity of sulfasalazine for the treatment of ankylosing spondylitis.
Search methods
Relevant randomised and quasi‐randomised trials in any language were sought using the following sources: CENTRAL (Cochrane Central Register of Controlled Trials, Issue 2, 2003), MEDLINE (1966 to June Week 4 2003), EMBASE (1980 to 2003 Week 26), CINAHL (1982 to June Week 3 2003) and the reference section of retrieved articles.
Selection criteria
We evaluated randomised and quasi‐randomised trials examining the efficacy of sulfasalazine on ankylosing spondylitis.
Data collection and analysis
Unblinded trial reports were reviewed independently by two reviewers according to the selection criteria. Disagreements on the inclusion of the studies were resolved, where necessary, by recourse to a third reviewer. The methodological quality of included trials were independently assessed by the same reviewers on randomization, concealment, blindness (participants, care providers and outcome investigators), description of withdrawals and drop‐outs and intention‐to‐treat analysis. The same reviewers independently entered the data extracted from the included trials, using RevMan double entry facility. Results were combined using weighted mean difference or standardised mean difference for continuous data, and relative risk for dichotomous data.
Main results
Twelve studies met the inclusion criteria but only eleven were included in the data analysis. The pooled analysis showed that the difference between intervention groups was significant only in erythrocyte sedimentation rate (ESR) (WMD ‐4.79, 95% CI ‐8.80 to ‐0.78) mm/h) and morning stiffness VAS‐100 mm (visual analogue scale 100 mm, where 0 = no stiffness and 100 = severe) (WMD ‐13.89, 95% CI ‐22.54 to ‐5.24), favouring SSZ over placebo. The trial with the largest sample (Clegg 1996) and that with the longest treatment duration (Kirwan 1993) had similar results. Both trials found that SSZ showed evidence of benefit in the occurrence of peripheral joint symptoms and peripheral responses in patients with peripheral arthritis. Nissila 1988 is the only trial in which SSZ showed benefit in primary outcome analyses, including back pain, chest expansion, occiput‐to‐wall test and patient's general well being. Compared with other trials, the patients in this trial had the shortest disease duration and the highest level of baseline ESR and contained the greatest proportion of patients with peripheral arthritis. Significantly more withdrawals for side effects (RR 1.50, 95% CI 1.04 to 2.15, NNH 23, 95% CI 10 to 288) and for any reason (RR 1.33, 95% CI 1.03 to 1.73, NNH 17, 95% CI 8 to 180) were found in SSZ compared with placebo group although severe side effects were rare (1 of the 469 patients taking SSZ).
Authors' conclusions
Across all AS patients, SSZ demonstrated some benefit in reducing ESR and easing morning stiffness, but no evidence of benefit in physical function, pain, spinal mobility, enthesitis, patient and physician global assessment. Patients at early disease stage, with higher level of ESR (or active disease) and peripheral arthritis might benefit from SSZ.
PICOs
Plain language summary
Sulfasalazine for ankylosing spondylitis
Does sulfasalazine work to treat ankylosing spondylitis and how safe is it?
To answer this question, scientists found and analyzed 11 research studies. These studies included almost 900 people with ankylosing spondylitis, most of them were male and 27 to 46 years old. People were either given sulfasalazine at 2‐3 g per day or were in another group that had a fake pill for 12 weeks to 3 years. This Cochrane review provides the best evidence we have today.
What is ankylosing spondylitis and why is sulfasalazine prescribed?
Ankylosing spondylitis (AS) is a type of arthritis usually in the joints and ligaments of the spine. It may also affect shoulders, hips, or other joints and cause tendonitis. Pain and stiffness occurs and limits movement in the back and affected joints. It can come and go, last for long periods, and be quite severe. Non‐steroidal anti‐inflammatory drugs (NSAIDs) are the main treatment for AS and can improve the symptoms of AS. But when NSAIDs are not working well disease modifying anti‐rheumatic drugs (DMARDs), such as sulfasalazine may be used. Side effects have been reported with sulfasalazine. Therefore, it is necessary to know how well sulfasalazine works and whether it is safe.
How well does it work?
Morning stiffness and the erythrocyte sedimentation rate/'sed' rate (ESR) decreased more in people taking sulfasalazine compared to those taking fake pills (lower ESRs usually mean less inflammation).
Morning stiffness decreased by 14 more points on a scale of 0 to 100 when taking sulfasalazine than fake pills.
Improvements in movement of the spine, pain, function (physical ability) and overall‐well being was about the same whether people took sulfasalazine or fake pills. But one study found that improvement did occur in people who had not had AS for very long, who had very active disease or peripheral arthritis (arthritis in arms and legs).
How safe is it?
People had side effects such as stomach upset, skin reactions/rashes and mouth sores.
More people stopped taking sulfasalazine because of the side effects than when taking fake pills.
14 out of 100 people stopped taking sulfasalazine because of the side effects.
9 out of 100 people stopped taking fake pills
What is the bottom line?
There is "gold" level of evidence that sulfasalazine improves morning stiffness and the erythrocyte sedimentation rate (ESR) in people with ankylosing spondylitis. It is not clear whether it improves pain, function (physical ability), movement of the spine and overall well being.
Side effects occur in some people and include stomach upset, skin rashes and mouth sores which may occasionally stop people from taking sulfasalazine. But severe side effects appear rare.
People with early ankylosing spondylitis, with active disease or peripheral arthritis may improve with sulfasalazine.
